Hostname: page-component-7479d7b7d-m9pkr Total loading time: 0 Render date: 2024-07-12T17:57:32.897Z Has data issue: false hasContentIssue false
  • English
  • Français

Recombinant activated factor VII in cardiac surgery

Published online by Cambridge University Press:  01 June 2007

M. Ranucci  and
G. Isgrò
M. Ranucci*
Affiliation:
Cardiothoracic Anaesthesia and Intensive Care Department, IRCCS Policlinico S. Donato, Italy
G. Isgrò
Affiliation:
Cardiothoracic Anaesthesia and Intensive Care Department, IRCCS Policlinico S. Donato, Italy
*
Correspondence to: Marco Ranucci, Head Cardiothoracic Anesthesia Dept, IRCCS Policlinico S. Donato, Via Morandi 30, 20097 San Donato Milanese, Milan (Italy). E-mail: cardioanestesia@virgilio.it; Tel: +39 02 52774320;Fax: +39 02 55602262
Get access

Summary

Background and objective

Recombinant activated factor VII (rFVIIa) is a pharmacologic compound approved for the use in patients with congenital or acquired hemophilia and inhibiting antibodies toward factor VIII or IX. In recent years its use has been proposed in surgical patients demonstrating a lifethreatening bleeding, refractory to the standard therapies. The present study is a review of the clinical information available on the use of rFVIIa in cardiac surgery patients.

Methods

Current literature was investigated using a Pubmed search with appropriate key words (rFVIIa OR recombinant activated factor VII AND cardiac surgery).

Results

35 articles were found. These are 11 case reports, 12 case series, 5 review articles, 3 retrospective studies, 2 letters to the Editor, and only one prospective, double-blinded, randomized clinical trial (RCT). The majority of the case reports and case series report a beneficial effect of this drug in the treatment of refractory bleeding. Comparative retrospective studies show conflicting results, and the only RCT demonstrate a significant reduction of allogeneic blood products use in patients treated with rFVIIa. No definitive information is available with respect to thromboembolic complications and general safety of this therapy.

Conclusions

rFVIIa is a promising agent for intractable bleeding in surgical patients. However, large prospective randomized trials are needed to define efficacy, dose, and potential side-effects.

Keywords

coagulation factorsblood transfusionssurgery
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 24 , Issue S40 , June 2007 , pp. 83 - 88
Copyright
Copyright © European Society of Anaesthesiology 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Levi, M, Peters, M, Büller, HR. Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: a systematic review. Crit Care Med 2005; 33: 883–890.CrossRefGoogle ScholarPubMed
2.Ahonen, J, Jokela, R. Recombinant factor VIIa for lifethreatening post-partum haemorrhage. Br J Anaesth 2005; 94: 592–595.CrossRefGoogle ScholarPubMed
3.Bouwmeester, FW, Jonkhoff, AR, Verheijen, RH, van Geijn, HP. Successful treatment of lifethreatening postpartum hemorrhage with recombinant activated factor VII. Obstet Gynecol 2003; 101: 1174–1176.Google ScholarPubMed
4.Danilos, J, Goral, A, Paluszkiewicz, P, Przesmycki, K, Kotarski, J. Successful treatment with recombinant factor VIIa for intractable bleeding at pelvic surgery. Obstet Gynecol 2003; 101: 1172–1173.Google ScholarPubMed
5.Dunkley, SM, Mackie, F. Recombinant factor VIIa used to control massive haemorrhage during renal transplantation surgery; vascular graft remained patent. Hematology 2003; 8: 263–264.CrossRefGoogle ScholarPubMed
6.Flynn, JD, Pajoumand, M, Jr.Camp, PC, Jahania, MS, Ramaiah, C, Akers, WS. Recombinant factor VIIa for refractory bleeding following orthotopic heart transplantation. Ann Pharmacother 2004; 38: 1639–1642.CrossRefGoogle ScholarPubMed
7.Gerlach, R, Marquardt, G, Wissing, H, Scharrer, I, Raabe, A, Seifert, V. Application of recombinant activated factor VII during surgery for a giant skull base hemangiopericytoma to achieve safe hemostasis. J Neurosurg 2002; 96: 946–948.CrossRefGoogle ScholarPubMed
8.Gielen-Wijffels, SE, van Mook, WN, van der Geest, S, Ramsay, G. Successful treatment of severe bleeding with recombinant factor VIIa after kidney transplantation. Intensive Care Med 2004; 30: 1232–1234.CrossRefGoogle ScholarPubMed
9.Heilmann, L, Wild, C, Hojnacki, B, Pollow, K. Successful treatment of lifethreatening bleeding after cesarean section with recombinant activated factor VII. Clin Appl Thromb Hemost 2006; 12: 227–229.CrossRefGoogle ScholarPubMed
10.Leibovitch, L, Kenet, G, Mazor, K et al. . Recombinant activated factor VII for lifethreatening pulmonary hemorrhage after pediatric cardiac surgery. Pediatr Crit Care Med 2003; 4: 444–446.CrossRefGoogle ScholarPubMed
11.Liem, KSAE, Biesma, DH, Ernst, SMPG, Schepens, MAAM. Recombinant activated factor VII for false aneurysms in patients with normal haemostatic mechanisms. Thromb Haemost 1999; 82: 150–151.Google ScholarPubMed
12.Price, G, Kaplan, J, Skowronski, G. Use of recombinant factor VIIa to treat lifethreatening non-surgical bleeding in a post-partum patient. Br J Anaesth 2004; 93: 928–930.CrossRefGoogle Scholar
13.Raux, M, Chiche, L, Vanhille, E, Riou, B. Recombinant activated factor VII to control massive postoperative bleeding after septic aortobifemoral grafting. Eur J Anesthesiol 2005; 22: 805–807.CrossRefGoogle ScholarPubMed
14.Stratmann, G, Russell, IA, Merrick, SH. Use of recombinant factor VIIa as a rescue treatment for intractable bleeding following repeat aortic arch repair. Ann Thorac Surg 2003; 76: 2094–2097.CrossRefGoogle ScholarPubMed
15.Vidal, MA, Sebastianes, C, Eizaga, R, Martinez, E, Torres, LM. Activated recombinant factor VII for bleeding after a kidney transplant. Rev Esp Anestesiol Reanim 2005; 52: 638–639.Google ScholarPubMed
16.Weilbach, C, Scheinichen, D, Juttner, B, Schurholz, T, Piepenbrock, S. Excessive blood loss after abdominal hysterectomy – use of recombinant factor VIIa. Anasthesiol Intensivmed Notfallmed Schmerzther 2004; 39: 672–675.CrossRefGoogle ScholarPubMed
17.Aggarwal, A, Malkovska, V, Catlett, JP, Alcorn, K. Recombinant activated factor VII (rFVIIa) as salvage treatment for intractable hemorrage. Thromb J 2004; 2: 9.CrossRefGoogle Scholar
18.Al Douri, M, Shafi, T, Al Khudairi, D et al. . Effect of the administration of recombinant activated factor VII (rFVIIa; NovoSeven) in the management of severe uncontrolled bleeding in patients undergoing heart valve replacement surgery. Blood Coagul Fibrinolysis 2000 (Suppl 1): S121–S127.CrossRefGoogle ScholarPubMed
19.Benharash, P, Bongard, F, Putnam, B. Use of recombinant factor VIIa for adjuntive hemorrhage control in trauma and surgical patients. Am Surg 2005; 71: 776–780.CrossRefGoogle Scholar
20.Carvalho, A, Leitao, J, Louro, E et al. . Small dose of recombinant factor VIIa (rFVIIa) to perform percutaneous liver biopsies in cirrhotic patients. Rev Esp Enferm Dig 2002; 94: 280–285.Google ScholarPubMed
21.DiDomenico, RJ, Massad, MG, Kpodonu, J, Navarro, RA, Geha, AS. Use of recombinant activated factor VII for bleeding following operations requiring cardiopulmonary bypass. Chest 2005; 127: 1828–1835.CrossRefGoogle ScholarPubMed
22.Egan, JR, Lammi, A, Schell, DN, Gillis, J, Nunn, GR. Recombinant activated factor VII in paediatric cardiac surgery. Intensive Care Med 2004; 30: 682–685.CrossRefGoogle ScholarPubMed
23.Etxaniz, Alvarez A, Pita Zapata, E, Rama Maceiras, P, Duro Tacon, J, Pose Cambeiro, P. Recombinant activated factor VII in the postanesthetic recovery unit: review of 16 cases. Rev Esp Anestesiol Reanim 2006; 53: 159–162.Google Scholar
24.Gala, B, Quintela, J, Aguirrezabalaga, J et al. . Benefits of recombinant activated factor VII in complicated liver transplantation. Transplant Proc 2005; 37: 3919–3921.CrossRefGoogle ScholarPubMed
25.Heisel, M, Nagib, M, Madsen, L, Alshiekh, M, Bendel, A. Use of recombinant factor VIIa (rFVIIa) to control intraoperative bleeding in pediatric brain tumor patients. Pediatr Blood Cancer 2004; 43: 703–705.CrossRefGoogle ScholarPubMed
26.Hyllner, M, Houltz, E, Jeppsson, A. Recombinant activated factor VII in the management of lifethreatening bleeding in cardiac surgery. Eur J Cardiothorac Surg 2005; 28: 254–258.CrossRefGoogle ScholarPubMed
27.Jr.Kaw, LL, Coimbra, R, Potenza, BM, Garfin, SR, Hoyt, DB. The use of recombinant factor VIIa for severe intractable bleeding during spine surgery. Spine 2004; 29: 1384–1387.CrossRefGoogle ScholarPubMed
28.Manning, BJ, Hynes, N, Courtney, DF, Sultan, S. Recombinant factor VIIa in the treatment of intractable bleeding in vascular surgery. Eur J Vasc Endovasc Surg 2005; 30: 525–527.CrossRefGoogle ScholarPubMed
29.O’ Connell, NM, Perry, DJ, Hodgson, AJ, O’Shaughnessy, DF, Laffan, MA, Smith, OP. Recombinant factor VIIa in the management of uncontrolled hemorrhage. Transfusion 2003; 43: 1711–1716.CrossRefGoogle ScholarPubMed
30.Park, P, Fewel, ME, Garton, HJ, Thompson, BG, Hoff, JT. Recombinant activated factor VII for the rapid correction of coagulopathy in nonhemophilic neurosurgical patients. Neurosurgery 2003; 53: 34–38.CrossRefGoogle ScholarPubMed
31.Raivio, P, Suojaranta-Ylinen, R, Kuitunen, AH. Recombinant factor VIIa in the treatment of postoperative hemorrhage after cardiac surgery. Ann Thorac Surg 2005; 80: 66–71.CrossRefGoogle ScholarPubMed
32.Tawfick, WA, Tawfik, S, Hynes, N, Mahendran, B, Sultan, S. Critical bleeding in vascular surgery: expanding the indication of recombinant activated factor VII. Vascular 2006; 14: 32–37.CrossRefGoogle ScholarPubMed
33.Tobias, JD, Simsic, JM, Weinstein, S, Schechter, W, Kartha, V, Michler, R. Recombinant factor VIIa to control excessive bleeding following surgery for congenital heart disease in pediatric patients. J Intensive Care Med 2004; 19: 270–273.CrossRefGoogle ScholarPubMed
34.Yan, Q, Chang, AC. Pharmacologic therapy for postoperative bleeding in children after cardiac surgery: when will the bleeding stop? Pediatr Crit Care Med 2004; 5: 297–298.CrossRefGoogle ScholarPubMed
35.Hendriks, HG, Meijer, K, de Wolf, JT et al. . Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study. Transplantation 2001; 71: 402–405.CrossRefGoogle ScholarPubMed
36.Karkouti, K, Beattie, WS, Wijeysundera, DN et al. . Recombinant factor VIIa for intractable blood loss after cardiac surgery: a propensity score-matched case-control analysis. Transfusion 2005; 45: 26–34.CrossRefGoogle ScholarPubMed
37.Niemann, CU, Behrends, M, Quan, D et al. . Recombinant factor VIIa reduces transfusion requirements in liver transplant patients with high MELD scores. Transfus Med 2006; 16: 93–100.CrossRefGoogle ScholarPubMed
38.von Heymann, C, Redlich, U, Jain, U et al. . Recombinant activated factor VII for refractory bleeding after cardiac surgery—a retrospective analysis of safety and efficacy. Crit Care Med 2005; 33: 2241–2246.CrossRefGoogle ScholarPubMed
39.Friederich, PW, Geerdink, MG, Spataro, M et al. . The effect of the administration of recombinant activated factor VII (NovoSeven) on perioperative blood loss in patients undergoing transabdominal retropubic prostatectomy: the PROSE study. Blood Coagul Fibrinolysis 2000; 11 (Suppl 1): S129–S132.CrossRefGoogle ScholarPubMed
40.Pihusch, M, Bacigalupo, A, Szer, J et al. . Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation. J Thromb Haemost 2005; 3: 1935–1944.CrossRefGoogle ScholarPubMed
41.Jeffers, L, Chalasani, N, Balart, L, Pyrsopoulos, N, Erhardtsen, E. Safety and efficay of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy. Gastroenterology 2002; 123: 118–126.CrossRefGoogle Scholar
42.Lodge, JP, Jonas, S, Jones, RM et al. . Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Liver Transpl 2005; 11: 973–979.CrossRefGoogle ScholarPubMed
43.Lodge, JP, Jonas, S, Oussoultzoglou, E et al. . Recombinant coagulation factor VIIa in major liver resection. A randomized, placebo-controlled, double-blind clinical trial. Anesthesiology 2005; 102: 269–275.CrossRefGoogle ScholarPubMed
44.Planinsic, RM, van der Meer, J, Testa, G et al. . Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transpl 2005; 11: 895–900.CrossRefGoogle ScholarPubMed
45.Shao, YF, Yang, JM, Chau, GY et al. . Safety and hemostatic effects of recombinant activated factor VII in cirrothic patients undergoing partial heaptectomy: a multicenter, randomized, double-blind, placebo- controlled trial. Am J Surg 2006; 191: 245–249.CrossRefGoogle Scholar
46.Raobaikady, R, Redman, J, Ball, JA, Maloney, G, Grounds, RM. Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial. Br J Anaesth 2005; 94: 586–591.CrossRefGoogle ScholarPubMed
47.Friederich, PW, Henny, CP, Messelink, EJ et al. . Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial. Lancet 2003; 361: 201–205.CrossRefGoogle ScholarPubMed
48.Diprose, P, Herbertson, MJ, O’ Shaughnessy, D, Gill, RS. Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study. Br J Anaesth 2005; 95: 596–602.CrossRefGoogle ScholarPubMed
49.Vincent, J-L, Rossaint, R, Riou, B, Ozier, Y, Zideman, D, Spahn, DR. Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding – a European perspective. Critical Care 2006; 10: R120.CrossRefGoogle ScholarPubMed
50.Trowbridge, CC, Stammers, AH, Ciccarelli, N, Klayman, M. Dose titration of recombinant factor VIIa using thromboelastograph monitoring in a child with hemophilia and high titer inhibitors to factor VIII: a case report and brief review. J Extra Corpor Technol 2006; 38: 254–259.CrossRefGoogle Scholar
51.Filsoufi, F, Castillo, JG, Rahmanian, PB, Scurlock, C, Fischer, G, Adams, DH. Effective management of refractory postcardiotomy bleeding with the use of recombinant activated factor VII. Ann Thorac Surg 2006; 82: 1779–1783.CrossRefGoogle ScholarPubMed
52.White, MC, Pryn, SJ, Monk, CR. Thrombogenic side-effects of recombinant factor VIIa after use in coronary artery bypass surgery. Anaesth Intensive Care 2006; 34: 664–667.CrossRefGoogle ScholarPubMed
53.McCall, P, Story, DA, Karapillai, D. Audit of factor VIIa for bleeding resistant to conventional therapy following complex cardiac surgery. Can J Anaesth 2006; 53: 926–933.CrossRefGoogle ScholarPubMed
54.von Heymann, C, Spies, C, Grubitzsch, H, Schonfeld, H, Sander, M, Volk, T. Bleeding after cardiac surgery: the role of recombinant factor VIIa. Hamostaseologie 2006; 26 3 Suppl 1: S77–S87.Google ScholarPubMed
55.Scarpelini, S, Rizoli, S. Recombinant factor VIIa and the surgical patient. Curr Opin Crit Care 2006; 12: 351–356.CrossRefGoogle ScholarPubMed
56.Grizelj, R, Vukovic, J, Filipovic-Grcic, B, Saric, D, Luetic, T. Successful use of recombinant activated FVII and aminocaproic acid in four neonates with lifethreatening hemorrhage. Blood Coagul Fibrinolysis 2006; 17: 413–415.CrossRefGoogle ScholarPubMed
57.Ozier, Y, Schlumberger, S. Pharmacological approaches to reducing blood loss and transfusion in the surgical patient. Can J Anaesth 2006; 53 6 Suppl: S21–S29.CrossRefGoogle ScholarPubMed
58.Romagnoli, S, Bevilacqua, S, Gelsomino, S et al. . Small-dose recombinant activated factor VII (NovoSeven) in cardiac surgery. Anesth Analg 2006; 102: 1320–1326.CrossRefGoogle ScholarPubMed
59.Oh, JJ, Akers, WS, Lewis, D, Ramaiah, C, Flynn, JD. Recombinant factor VIIa for refractory bleeding after cardiac surgery secondary to anticoagulation with the direct thrombin inhibitor lepirudin. Pharmacotherapy 2006; 26: 569–577.CrossRefGoogle ScholarPubMed
60.Bishop, CV, Renwick, WE, Hogan, C, Haeusler, M, Tuckfield, A, Tatoulis, J. Recombinant activated factor VII: treating postoperative hemorrhage in cardiac surgery. Ann Thorac Surg 2006; 81: 875–879.CrossRefGoogle ScholarPubMed
61.Levy, JH. Massive transfusion coagulopathy. Semin Hematol 2006; 43 1 Suppl 1: S59–S63.CrossRefGoogle ScholarPubMed
62.Despotis, G, Avidan, M, Lublin, DM. Off-label use of recombinant factor VIIA concentrates after cardiac surgery. Ann Thorac Surg 2005; 80: 3–5.CrossRefGoogle ScholarPubMed
63.Gowers, CJ, Parr, MJ. Recombinant activated factor VIIa use in massive transfusion and coagulopathy unresponsive to conventional therapy. Anaesth Intensive Care 2005; 33: 196–200.CrossRefGoogle ScholarPubMed
64.Hein, OV, von Heymann, C, Morgera, S, Konertz, W, Ziemer, S, Spies, C. Protracted bleeding after hirudin anticoagulation for cardiac surgery in a patient with HIT II and chronic renal failure. Artif Organs 2005; 29: 507–510.CrossRefGoogle Scholar
65.Tofil, NM, Winkler, MK, Watts, RG, Noonan, J. The use of recombinant factor VIIa in a patient with Noonan syndrome and lifethreatening bleeding. Pediatr Crit Care Med 2005; 6: 352–354.CrossRefGoogle Scholar
66.Kogan, A, Berman, M, Stein, M, Vidne, BA, Raanani, E. Recombinant factor VIIa use in cardiac surgery – expanding the arsenal therapy for intractable bleeding? J Cardiovasc Surg (Torino) 2004; 45: 569–571.Google ScholarPubMed
67.Yilmaz, BT, Alioglu, B, Ozyurek, E, Akay, HT, Mercan, S, Ozbek, N. Successful use of recombinant factor VIIa (NovoSeven) during cardiac surgery in a pediatric patient with Glanzmann thrombasthenia. Pediatr Cardiol 2005; 26: 843–845.CrossRefGoogle Scholar
68.Herbertson, M. Recombinant activated factor VII in cardiac surgery. Blood Coagul Fibrinolysis 2004; 15 (Suppl 1): S31–S32.CrossRefGoogle ScholarPubMed
69.Pychynska-Pokorska, M, Moll, JJ, Krajewski, W, Jarosik, P. The use of recombinant coagulation factor VIIa in uncontrolled postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass. Pediatr Crit Care Med 2004; 5: 246–250.CrossRefGoogle ScholarPubMed